Mechanisms Of Infection Triggered Renal Vasculitis
Funder
National Health and Medical Research Council
Funding Amount
$413,900.00
Summary
Kidney disease, including glomerulonephritis, is an important cause of ill-health in Australia. Some forms of kidney inflammation are linked to infection, but we don�t understand why. This project explores products from bacteria, particularly S.aureus, to work out how bacterial infection affects a form of kidney inflammation - ANCA-associated glomerulonephritis. It will establish how infection related signals activate local and immune cells, and define links between infection and the disease.
The Diamond Cohort Study - Long Term Outcomes Of Depressive Symptoms In Primary Care
Funder
National Health and Medical Research Council
Funding Amount
$567,538.00
Summary
The diamond study follows what happens to almost 800 people with depressive symptoms whom attend general practice for care over 5 years of their life. This study will map the severity of depressive symptoms, life circumstances, use of health care services and treatments and allow us to understand factors associated with relapse and recovery from depression in order to improve care. This will assist us to develop models of care that better suit the needs of people experiencing depressive symptoms ....The diamond study follows what happens to almost 800 people with depressive symptoms whom attend general practice for care over 5 years of their life. This study will map the severity of depressive symptoms, life circumstances, use of health care services and treatments and allow us to understand factors associated with relapse and recovery from depression in order to improve care. This will assist us to develop models of care that better suit the needs of people experiencing depressive symptoms.Read moreRead less
A Randomised Placebo-controlled Trial Of Antibiotics To Prevent Urinary Tract Infection In Children
Funder
National Health and Medical Research Council
Funding Amount
$735,000.00
Summary
This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this ....This study is needed to determine whether a common clinical practice long-term antibiotic treatment for children following urinary tract infection (UTI) - is safe and effective in preventing further UTI and if so, whether all appropriate children are being treated. UTI will affect about 10% of Australian children by high school age (88,000 children per year). Because UTI may damage the kidneys, the management priority for children with UTI has been prevention of further infection. Currently this means the identification of children thought to be most at risk of recurrent UTI by renal tract imaging. Those found to have reflux of urine from the bladder to the kidney (present in about 30% of those with UTI) are then placed on antibiotics fro 2-5 years. Unfortunately there has never been a properly designed trial to test whether antibiotics do really prevent UTI and if so, whether children with reflux are the appropriate and only group requiring treatment. Long term antibiotics may in fact do more harm than good because of side effects like skin, bowel and blood problems and because resistant bacteria may develop. The design of this study involves the random allocation of placebo or antibiotic (cotrimoxazole, the usual antibiotic given in this case) to about 800 children after their first symptomatic UTI. These children are treated and followed for one year to determine the rate of futher UTI in both groups. Any difference in outcome between the two groups of children will be because of the antibiotic treatment. This study may prove long-term antibiotics are ineffective and therefore should not be routinely used. In this case investigation of children to detect vesicoureteric reflux would serve little purpose and should be abandoned. Alternatively antibiotic treatment may be shown as effective treatment for preventing further UTI and in this case the study will clearly identify those children who will benefit.Read moreRead less
Modelling The Effects Of Immunity On Influenza Transmission - Implications For Prevention And Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$275,767.00
Summary
There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our proj ....There is uncertainty about how many people can be infected by a single person with influenza at the start of an outbreak. Some data suggest that a single generation of transmission can infect 10-20 other people. With such a rate of growth (ie 10-20 fold every 3 days) the spread of an influenza outbreak is virtually unstoppable. Other data suggest that each person with influenza infects less than 2 other people on average. With such a lower rate of growth, control would be more feasible. Our project will use data from historic and contemporary outbreaks of influenza and build mathematical models to explain the rate of growth of an influenza outbreak in terms of: 1. The proportion of people exposed to influenza who do not become ill (although there can be evidence of infection if careful studies are made). This proportion is about 33%. 2. The proportion of people who are protected from influenza by immunity, whether induced by vaccination or by past exposure to natural influenza infection (this can vary from 0% in isolated populations which have not seen influenza for many years up to 80 or 90% in urbanised populations that are exposed to influenza almost every season). 3. Different rates of contact between different people and groups of people - some may be exposed so often that their immunity is boosted regularly without them becoming severely ill; others, living in more isolated circumstances, may be rarely exposed, but when they are, they are more likely to become severely ill. 4. The effects of influenza vaccine in inducing protective immunity - it is well known that there is good protection if the vaccine is well matched to the circulating virus. 5. The effects of live virus infection in inducing (short-lived) protection against a wider range of influenza viruses. Our model results will be used to guide vaccine design and pandemic planning.Read moreRead less
Development Of Antimicrobial Peptides Targeting Oral Pathogenic Bacteria
Funder
National Health and Medical Research Council
Funding Amount
$663,350.00
Summary
The bacterial associated oral diseases; periodontitis and caries are major public health problems. The prevalence of these diseases and increasing bacterial antibiotic resistance has meant there is a need to develop new therapies. This project addresses this by modifying a novel class of antibiotics/antiseptics �antimicrobial peptides� to target oral bacteria and testing them using a newly developed screening method. This project will lead to new therapies for periodontitis and caries.
A Study To Investigate Alternative Regimens For Pneumococcal Vaccination Of Infants In A Developing Country
Funder
National Health and Medical Research Council
Funding Amount
$1,622,210.00
Summary
Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver thi ....Streptococcus pneumoniae (Pnc) is the leading vaccine preventable cause of serious infection in infants. The current Pnc conjugate vaccine is very expensive (approximately USD $200-infant) so it is unlikely to be affordable for most developing countries. Moreover, as health care access in developing countries may be episodic and unreliable, many children do not receive either complete or timely vaccine courses. Therefore, it is important to investigate affordable and flexible ways to deliver this vaccine, which are safe and effective. A recent WHO-GAVI meeting to address impediments to the introduction of these vaccines in developing countries recognized the need to evaluate other regimens of Pnc conjugate vaccine as an important research priority. This study has been deliberately formulated with that need in mind. The site for this research is Fiji. Although health services are good, Pnc disease, particularly pneumonia, remains the commonest cause of childhood morbidity and mortality. Fiji has good vaccine coverage and was the first Pacific country to introduce Hib vaccine. The arrival of the new, expensive Pnc conjugate vaccine presents a dilemma for Fiji and many similar countries. The expense of this vaccine would consume a large portion of the health budget. This study has two components: 1. A Phase 2 immunogenicity study (involving 750 infants) to evaluate regimens using reduced numbers of doses of Pnc conjugate vaccine, and using timing of dosing and combinations with the Pnc polysaccharide (PS) vaccine that may be more suited to the epidemiology of Pnc disease in developing countries. 2. An epidemiological study will measure the burden of invasive Pnc disease and pneumonia in Fiji. This will be part of a global effort to address these issues, and will be used to develop rapid assessment tools for these diseases in developing countries. We will seek cofounding for this component.Read moreRead less
Determination Of Irradiation Dose Efficacy For Use In Impaction Grafting At Revision Joint Replacement
Funder
National Health and Medical Research Council
Funding Amount
$411,517.00
Summary
Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence ....Primary hip replacement is a successful intervention for hip disease, but 10-15% of hip prostheses fail and require revision surgery within 10-15 years. At the time of revision, significant bone loss around the failed prosthesis is not uncommon. A bone reconstruction procedure, called impaction grafting, where donor bone is minced and placed in the areas of deficient bone before implanting the new prosthesis, has shown to give good results at more than ten years in some centres. A high incidence of early complications of this procedure have included loss of fixation within the bone. Fracture of the bone around prostheses has also reported in some centres. These events require more surgery, putting the patient at higher risk greater complications and longer rehabilitations. Recent improvements in surgical technique and donor bone preparation have improved results. A current debate questions whether the dose of irradiation can be reduced from 25 kGy, while maintaining sterility of allografts. The risk of bacterial contamination in allografts is low, and irradiation reduces the mechanical strength of the graft, contributing to complications when irradiated bone is used. The benefits of decontaminating the bone may be outweighed by the higher risk for failure due to poor bone quality and resulting prosthesis instability. We will use ISO standards to test the validity of radiation dose for sterilising bone ex vivo. In the absence of controlled human studies, our aim is also to compare the results of impaction grafting with non-irradiated bone versus bone irradiated at current doses used by Australian bone banks, and lower doses indicated by ex vivo testing. We will use a large animal model of revision hip replacement, with precise measures of prosthesis stability. The results of this study will guide clinical decisions regarding the efficacy of current bone graft preparation procedures and the use of irradiated bone in human hip replacement surgery.Read moreRead less
The Role Of Renal Dendritic Cells In Infection And Immunity Under Immunosuppression
Funder
National Health and Medical Research Council
Funding Amount
$475,143.00
Summary
Kidney transplantation is the best treatment for kidney failure but it is frequently complicated by bacterial and viral infections that can cause rejection and may cause loss of the kidney. This grant will study the role that dendritic cells in the kidney play in causing rejection and preventing infection. With the knowledge gained from these studies, we will be able to discover new ways to prevent rejection and treat infections of the kidney post transplant.
Mechanisms Underlying APOBEC3G Restriction Of HIV-1
Funder
National Health and Medical Research Council
Funding Amount
$540,075.00
Summary
In the fight against worldwide HIV-AIDS, understanding natural cell defenses to the HIV virus may identify new virus targets and strategies to block HIV in humans. Here, we will use state-of-the-art, high resolution, fluorescent microscopy to understand how the recently identified cell protein, APOBEC3G, blocks the HIV life cycle in human cells. We anticipate that APOBEC3G will stop HIV from invading the nucleus of human cells to defend against HIV, a strategy we can apply to new therapies.
Randomised Double-blind Placebo-controlled Trial Of Aspirin In Primary Prevention Of CVD Events Or Dementia In The Aged.
Funder
National Health and Medical Research Council
Funding Amount
$3,532,500.00
Summary
The single most important risk factor for cardiovascular disease is age. All men aged 75 years have a 10-15% risk of having a stroke or heart attack in the next 5 years. Low dose aspirin has been shown to prevent further strokes and heart attacks in people who have already had one. It has been also shown to protect people who have not had a heart attack or stroke but who are at increased risk. Given that the elderly are at increased risk why do we need to do a trial in this particular group? The ....The single most important risk factor for cardiovascular disease is age. All men aged 75 years have a 10-15% risk of having a stroke or heart attack in the next 5 years. Low dose aspirin has been shown to prevent further strokes and heart attacks in people who have already had one. It has been also shown to protect people who have not had a heart attack or stroke but who are at increased risk. Given that the elderly are at increased risk why do we need to do a trial in this particular group? The reason is that relatively few elderly patients were included in the previous prevention trials. Also while the elderly may have the most to gain from treatment, they also have the most to lose because they are more likely to suffer from side-effects. Aspirin prevents heart attacks by stopping clots forming in blood vessels. This also means that people taking it have an increased tendency to bleed. Thus though it may prevent strokes due to clots it may also increase the risk of strokes caused by bleeding. Bleeding from the gut is another major problem as aspirin tends to erode the lining of the stomach. Minor bleeding from the gut can also lower blood oxygen carrying capacity which may exacerbate other diseases associated with ageing, e.g. heart failure. Dementia may be caused by repeated clots in small or large vessels. Dementia is a particular problem in the elderly affecting 10% of 85 year olds. It is a major cause of loss of quality of life and a significant cost to the community. Aspirin may reduce the progression of such a disease leading to a maintained quality of life (QOL) for individuals and their families. As our age increases our years of life remaining decreases. This is self-evident. Thus the potential to add years to life reduces and the potential of diseases to adversely affect quality of life becomes more important. Thus it may be more important to prevent a nonfatal stroke that leads to institutionalisation than a fatal stroke. Hence QOL will be assessed.Read moreRead less